Abstract
One histologic subtype of ovarian carcinoma, ovarian endometrioid adenocarcinoma (OEA), frequently harbors mutations that constitutively activate Wnt/beta-catenin-dependent signaling. We now show that defects in the PI3K/Pten and Wnt/beta-catenin signaling pathways often occur together in a subset of human OEAs, suggesting their cooperation during OEA pathogenesis. Deregulation of these two pathways in the murine ovarian surface epithelium by conditional inactivation of the Pten and Apc tumor suppressor genes results in the formation of adenocarcinomas morphologically similar to human OEAs with 100% penetrance, short latency, and rapid progression to metastatic disease in upwards of 75% of mice. The biological behavior and gene expression patterns of the murine cancers resemble those of human OEAs with defects in the Wnt/beta-catenin and PI3K/Pten pathways.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenocarcinoma, Clear Cell / genetics
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Adenocarcinoma, Clear Cell / metabolism
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Adenocarcinoma, Clear Cell / pathology
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Adenocarcinoma, Mucinous / genetics
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Adenocarcinoma, Mucinous / metabolism
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Adenocarcinoma, Mucinous / pathology
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Adenomatous Polyposis Coli Protein / genetics
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Adenomatous Polyposis Coli Protein / physiology
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Animals
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Carcinoma, Endometrioid / genetics
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Carcinoma, Endometrioid / metabolism
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Carcinoma, Endometrioid / pathology
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Cystadenocarcinoma, Serous / genetics
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Cystadenocarcinoma, Serous / metabolism
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Cystadenocarcinoma, Serous / pathology
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Disease Models, Animal*
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Epithelium / metabolism
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Epithelium / pathology
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic
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Humans
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Mice
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Mutation
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Neoplasm Staging
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Oligonucleotide Array Sequence Analysis
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Ovarian Neoplasms / genetics*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Ovary / metabolism
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Ovary / pathology
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PTEN Phosphohydrolase / genetics*
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PTEN Phosphohydrolase / physiology
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Phosphatidylinositol 3-Kinases / genetics*
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Phosphatidylinositol 3-Kinases / metabolism
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Signal Transduction*
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Survival Rate
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
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Wnt1 Protein / genetics*
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Wnt1 Protein / metabolism
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beta Catenin / genetics*
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beta Catenin / metabolism
Substances
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Adenomatous Polyposis Coli Protein
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Tumor Suppressor Protein p53
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Wnt1 Protein
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beta Catenin
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Phosphatidylinositol 3-Kinases
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PTEN Phosphohydrolase